Neurabins recruit protein phosphatase-1 and inhibitor-2 to the actin cytoskeleton.

Full Abstract

Inhibitor-2 (I-2) bound protein phosphatase-1 (PP1) and several PP1-binding proteins from rat brain extracts, including the actin-binding proteins, neurabin I and neurabin II. Neurabins from rat brain lysates were sedimented by I-2 and its structural homologue, I-4. The central domain of both neurabins bound PP1 and I-2, and mutation of a conserved PP1-binding motif abolished neurabin binding to both proteins. Microcystin-LR, a PP1 inhibitor, also attenuated I-2 binding to neurabins. Immunoprecipitation of neurabin I established its association with PP1 and I-2 in HEK293T cells and suggested that PP1 mediated I-2 binding to neurabins. The C terminus of I-2, although not required for PP1 binding, facilitated PP1 recruitment by neurabins, which also targeted I-2 to polymerized F-actin. Mutations that attenuated PP1 binding to I-2 and neurabin I suggested distinct and overlapping sites for these two proteins on the PP1 catalytic subunit. Immunocytochemistry in epithelial cells and cultured hippocampal neurons showed that endogenous neurabin II and I-2 colocalized at actin-rich structures, consistent with the ability of neurabins to target the PP1.I-2 complex to actin cytoskeleton and regulate cell morphology.

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Author information

Author/s: Terry-Lorenzo, Ryan T (RT); Elliot, Elizabeth (E); Weiser, Douglas C (DC); Prickett, Todd D (TD); Brautigan, David L (DL); Shenolikar, Shirish (S);

Affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Grants: GM56362 (Agency:United States NIGMS) ; NS41063 (Agency:United States NINDS)

Journal and publication information

Publication Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of biological chemistry (J Biol Chem), published in United States. (Language: eng)

Reference: 2002-Nov; vol 277 (issue 48) : pp 46535-43

Dates: Created 2002/11/26; Completed 2003/01/08; Revised 2007/11/15;

PMID: 12270929, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actins - metabolism
Animals
Base Sequence
Catalytic Domain
Cells, Cultured
Chromosomal Proteins, Non-Histone
Cytoskeleton - metabolism
DNA Primers
Hippocampus - cytology; metabolism
Humans
Immunohistochemistry

Microcystins
Microfilament Proteins - genetics; metabolism; physiology
Mutagenesis, Site-Directed
Nerve Tissue Proteins - genetics; metabolism; physiology
Peptides, Cyclic - metabolism; pharmacology
Phosphoprotein Phosphatases - antagonists & inhibitors; metabolism
Protein Binding
Protein Phosphatase 1
Proteins - chemistry; metabolism
Rats
Transcription Factors

Associated Chemicals: Actins (0) ; Chromosomal Proteins, Non-Histone (0) ; DNA Primers (0) ; Microcystins (0) ; Microfilament Proteins (0) ; Nerve Tissue Proteins (0) ; Peptides, Cyclic (0) ; Proteins (0) ; SET protein, human (0) ; Transcription Factors (0) ; neurabin (0) ; cyanoginosin LR (101043-37-2) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Protein Phosphatase 1 (EC 3.1.3.16)

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